Low-Dose Anticoagulation for Secondary Prevention in Acute Coronary Syndrome

After acute coronary syndrome (ACS), long-term dual antiplatelet therapy with acetylsalicylic acid and a P2Y12 platelet receptor antagonist is the standard of care for secondary prevention. Despite the introduction of more potent P2Y12 receptor antagonists, the risk of a recurrent vascular event within 12 months remains at approximately 10%, indicating a need for improved secondary prevention strategies. A recent phase III trial found that addition of a third antiplatelet agent, vorapaxar, in patients with atherosclerosis might benefit those who have previously experienced a myocardial infarction, although a trial in patients with ACS found this strategy led to increased bleeding without significant efficacy improvement. Previously, data from patients with ACS given vitamin K antagonists in addition to acetylsalicylic acid demonstrated significant reductions in vascular events, but this was associated with an unacceptable bleeding risk. As expected, phase II trials of newer oral anticoagulants in addition to dual antiplatelet therapy also found increased bleeding risk, with only the direct factor Xa inhibitors apixaban and rivaroxaban continuing to phase III. The phase III trial of full-dose apixaban was stopped early for safety concerns, because the major bleeding rates were significantly increased with minimal improvement in efficacy. However, the phase III trial of low-dose rivaroxaban demonstrated a significantly reduced incidence of recurrent vascular events without an increased risk of fatal bleeding. In conclusion, these trials underline the potential importance of optimal dose selection in phase III studies and suggest that the long-term use of low-dose anticoagulation, together with dual antiplatelet therapy, might have a role in secondary prevention after ACS.